Nazarov reagent

ETHYL 3-OXO-4-PENTENOATE (NAZAROVS REAGENT) (4-Pentenoic acid, 3-oxo-, ethyl ester)... 

Bodalski, R., Pietrusiewicz, K.M., Monkiewicz, J., and Koszuk, J., A new efficient synthesis of substituted Nazarov reagents. A Wittig-Homer-Em-mons approach, Tetrahedron Lett., 2287, 1980. 

An interesting alternative intramolecular cyclisation was discovered by Jprgensen and co-workers [187]. Although not strictly exploiting an enamine intermediate, the transformation represents a secondary amine catalysed Morita-Baylis-Hillman reaction leading to a series of highly functionalised cyclohexene products. Reaction of the Nazarov reagent 137 with a,P-unsaturated aldehydes in the presence of the diarylprolinol ether 30 led to the cyclohexene products 138 (49-68% yield 86-96% ee) via a tandem Michael/Morita-Baylis-Hillman reaction (Scheme 54). 

Nazarov reagents by means of a Wadsworth-Emmons olef ination. ... 

A similar coupling with a,p-unsaturated acid chlorides provides p-silyl divinyl ketones (Nazarov reagents). These ketones cyclize in the presence of a Lewis acid, particularly BF3 etherate, to cyclopentenones, generally with retention of the silyl group. 

Divinyl ketones.1 These butadienes react with aromatic aldehydes in the presence of MgBr2-0(C2H3)2 or ZnCl2 to furnish divinyl ketones (Nazarov reagents). 

Anionic polycyclization to a steroid.2 When treated with Cs2C03, 2-meth-oxycarbonylcyclohexenone (1) and the Nazarov reagent 2 undergo a Michael reaction followed by aldol condensation to give a tetracyclic adduct (3), which undergoes decarboalkoxylation (TsOH) to give the steroid derivative 4 in 47% overall yield. 

Lavallee, J.-R, Spino. C.. Ruel. R.. Hogan. K.T., and Deslongchamps, P, Stereoselective synthesis of cw-decalins via Diels-Alder and double Michael addition of substituted Nazarov reagents. Can. J. Chem., 70, 1406. 1992. 

An interesting strategy for convergent steroid synthesis has been reported by Deslongchamps based on Pd-catalyzed decarboxylation-Michael addition of allyl -keto ester (bicyclic Nazarov reagent) 605 to cyclohexanone 604. The first intermolecular Michael addition of the Pd-enolate, generated from 605, to 604 afforded 606. Further intramolecular Michael addition constructed the steroid skeleton 607, and the tetracycle 608 was obtained by jS-H elimination [218]. 

However, when an aryl substituent was introduced at the end of the Michael acceptor moiety of the Nazarov reagent employed, the reaction was found to... 

Scheme 7.29 Enantioselective formal [3 + 3] cycloaddition between Nazarov reagents and a,3-unsaturated aldehydes.

Scheme 7.30 Enantioselective Michael/Michael cascade using Nazarov reagents.

In a similar context, y,5-unsaturated p-ketoesters (Nazarov reagents) have also been employed as suitable functionalized Michael donor substrates for a Michael/Michael cascade reaction with nitroalkenes using, in this case, Takemoto s catalyst 68a (Scheme 7.65). This reaction proceeded in a tandem... 

A similar reaction was also reported by Jprgensen s group regarding the addition of Nazarov reagents (75) to enals (15). The reaction furnishes highly substituted cyclohexanones in high yields and stereoselectivities via an organocatalytic tandem Michael/Morita-Baylis-Hillman reaction catalyzed by the diphenylprolinol derivative VII [50]. 

Solid-phase techniques are also used for synthesis of compounds with trans-decalin motif where the Robinson annulation is used for synthesis of some natural product inspired structures such as that of 75. The protocol uses an immobilized solid phase bound Nazarov reagent that reacts with the enamine of the starting ketone under basic conditions. After cyclization the product is released from the solid phase by using TBAF at room temperature overnight. For the products 75a-c only one stereoisomer was formed (de > 98%) with modest 22-38% yields. 

Similar conditions were applied by Gong et al. to the asymmetric formal [3 + 3] cycloaddition of a,p-unsaturated aldehydes with Nazarov reagents bearing an aryl group at C5, which, after oxidation, afforded the corresponding 3,4-dihydropyranones in good yields combined with excellent enantioselectivities of up to 97% ee. The best results are collected in Scheme 6.23. 

Scheme 6.23 Formal [3 + 3] cycloadditions of a,P-unsaturated aldehydes with Nazarov reagents.

New applications of the Wittig and Wittig-Horner reactions include two related preparations of substituted y,5-unsaturated /3-ketoesters (Nazarov reagents) from ethyl 4-bromo-2-oxobutanoate. ... 

Scheme 3.76 Exo-selective Diels-Alder reaction with the Nazarov reagent.

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